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Tacrolimus analysis: A comparison of different methods and matrices

Warty, V and Zuckerman, S and Venkataramanan, R and Lever, W and Chao, J and McKaveney, T and Fung, J and Starzl, T (1995) Tacrolimus analysis: A comparison of different methods and matrices. Therapeutic Drug Monitoring, 17 (2). 159 - 167. ISSN 0163-4356

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Abstract

We determined the trough blood and plasma concentrations of tacrolimus from the day of transplantation through 30 days posttransplantation in four liver and four kidney transplant patients by three different methods. The first method involved a solid phase extraction of the blood or plasma using Sep-Pak columns (SPs) followed by quantitation of tacrolimus using an enzyme-linked immunosorbent assay (ELISA); the second method involved a liquid-liquid extraction using methylene chloride (MC) followed by quantitation of tacrolimus using the ELISA, and the third method involved a high-performance liquid chromatography (HPLC) fractionation of the extract obtained from the solid-phase extraction and quantitation of tacrolimus in the fractions by ELISA. The trough plasma tacrolimus concentrations ranged from 0.1 to 5.2 ng/ml. While the trough plasma concentrations of tacrolimus were similar and independent of the method of analysis in kidney transplant patients and in liver transplant patients with normal biochemical profile, in patients with liver dysfunction, tacrolimus plasma concentrations were higher when measured by SP-ELISA and MC-ELISA methods as compared to the HPLC-ELISA method. In plasma samples obtained from liver transplant patients with liver dysfunction, the presence of some metabolites that cross-reacted with the antibody used in the ELISA could be documented in the HPLC fraction corresponding to the metabolites. This indicates that while tacrolimus metabolites that cross-react significantly with the antibody used in the ELISA do not accumulate in kidney transplant patients, they can appear in the plasma of patients with liver dysfunction. The trough blood tacrolimus concentrations in patients were significantly higher than the corresponding plasma concentrations and ranged from 1.4 to 107 ng/ml. The trough blood tacrolimus concentrations were similar and independent of the method of analysis in kidney and liver transplant patients, suggesting unchanged tacrolimus to be the major component in the blood. The HPLC fractions corresponding to the metabolites of tacrolimus did not contain any components that cross-reacted with the antibody used. This study documents that the methods used in this study for the analysis of blood concentrations of tacrolimus appear to be specific for the parent tacrolimus and can be used in future pharmacokinetic and clinical studies. © 1995 Raven Press, Ltd., New York.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Warty, V
Zuckerman, S
Venkataramanan, Rrv@pitt.eduRV
Lever, W
Chao, J
McKaveney, T
Fung, J
Starzl, Ttes11@pitt.eduTES11
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1995
Date Type: Publication
Journal or Publication Title: Therapeutic Drug Monitoring
Volume: 17
Number: 2
Page Range: 159 - 167
DOI or Unique Handle: 10.1097/00007691-199504000-00010
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0163-4356
Other ID: uls-drl:31735062126622, Starzl CV No. 1812
Date Deposited: 08 Apr 2010 17:30
Last Modified: 02 Feb 2019 14:56
URI: http://d-scholarship.pitt.edu/id/eprint/5198

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